This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alterations of signal transduction pathways play a significant role in the growth and metastasis of human cancers. We focus on the Her2/neu receptor tyrosine kinase, a member of the EGFR growth factor receptor family, which is gene amplified and activated in about 25% of human breast cancer cases. Several drugs that target Her2/neu are used in the treatment of Her2-positive breast cancer, such as a monoclonal antibody to the extracellular portion of the receptor or small molecule kinase inhibitors, but resistance to these drugs has frequently been seen in patients. Better understanding of Her2/neu and the downstream signal transduction pathways it uses will provide improved treatment for breast cancer patients. Our lab studies signal transduction pathways in breast cancer using a variety of approaches involving biochemistry, proteomics, and cell biology.